Loss of Drp1 function alters OPA1 processing and changes mitochondrial membrane organization
| Autor: | Stephan Frank, Ansgar Santel, Petr Hájek, Kristin Möpert, Jörg Kaufmann, Christiane Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Dynamins
endocrine system MFN2 Biology Mitochondrial apoptosis-induced channel Membrane Fusion Mitochondrial Membrane Transport Proteins GTP Phosphohydrolases Mitochondrial Proteins Mitochondrial membrane transport protein Prohibitins MFN1 Animals Humans RNA Small Interfering Inner mitochondrial membrane Membrane Proteins Membrane Transport Proteins Cell Biology eye diseases Mitochondrial membrane organization Cell biology Mitochondria Isoenzymes mitochondrial fusion Gene Knockdown Techniques Mitochondrial Membranes biology.protein Mitochondrial fission RNA Interference Microtubule-Associated Proteins HeLa Cells |
| Popis: | RNAi mediated loss of Drp1 function changes mitochondrial morphology in cultured HeLa and HUVEC cells by shifting the balance of mitochondrial fission and fusion towards unopposed fusion. Over time, inhibition of Drp1 expression results in the formation of a highly branched mitochondrial network along with “bulge”-like structures. These changes in mitochondrial morphology are accompanied by a reduction in levels of Mitofusin 1 (Mfn1) and 2 (Mfn2) and a modified proteolytic processing of OPA1 isoforms, resulting in the inhibition of cell proliferation. In addition, our data imply that bulge formation is driven by Mfn1 action along with particular proteolytic short-OPA1 (s-OPA1) variants: Loss of Mfn2 in the absence of Drp1 results in an increase of Mfn1 levels along with processed s-OPA1-isoforms, thereby enhancing continuous “fusion” and bulge formation. Moreover, bulge formation might reflect s-OPA1 mitochondrial membrane remodeling activity, resulting in the compartmentalization of cytochrome c deposits. The proteins Yme1L and PHB2 appeared not associated with the observed enhanced OPA1 proteolysis upon RNAi of Drp1, suggesting the existence of other OPA1 processing controlling proteins. Taken together, Drp1 appears to affect the activity of the mitochondrial fusion machinery by unbalancing the protein levels of mitofusins and OPA1. |
| Databáze: | OpenAIRE |
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